Fig. 5.

Validation of the miR-148/152–SPIN1–ABCB4/CYP2C8/UGT2B4/UGT2B17 signaling in xenograft tumors. a-c Expression levels of miR-148a-3p, miR-148b-3p or miR-152-3p were inversely related with SPIN1 mRNA expression in MCF-7/ADM xenograft tumors (n = 20). d-e SPIN1 protein expression in ten xenograft tumors was detected by immunohistochemistry. Representative images were shown. f Expression of miR-148a-3p (r = − 0.7478, P = 0.0162), miR-148b-3p (r = − 0.6524, P = 0.0473) or miR-152-3p (r = − 0.8512, P = 0.0032) were inversely related with SPIN1 protein expression. g-j A positive relationship between mRNA expression of SPIN1 and ABCB4, CYP2C8, UGT2B4 and UGT2B17 was observed (n = 20). k Three tumors with high expression of SPIN1 and the other three with low SPIN1 expression were selected for Western blot analysis. Tumors with high SPIN1 protein levels tend to show high expression of ABCB4, CYP2C8, UGT2B4 and UGT2B17. l A schematic model of miR-148/152–SPIN1–ABCB4/CYP2C8/UGT2B4/UGT2B17 regulation of breast cancer chemoresistance. SPIN1, which is direct target of miR-148a-5p/148b-5p/152-5p, promotes chemoresistance via upregulating ABCB4, CYP2C8, UGT2B4 and UGT2B17